阅读说明：本技术 用于牙龈炎检测的大动态范围检测器 (Large dynamic range detector for gingivitis detection ) 是由 O·T·J·A·弗梅尤伦 A·J·戴维 S·C·迪恩 于 2019-09-02 设计创作，主要内容包括：一种用于检测组织炎症,特别是牙龈炎的系统(100),包括：光发射器(102),被配置为在用户嘴内的组织区域处发光；至少四个波长敏感光电检测器(110,112,114和116),被配置为检测通过组织区域漫反射的光学信号,至少四个波长敏感光电检测器中的每个波长敏感光电检测器包括滤波器(BPF1,BPF2,BPF3和BPF4)和光电二极管(D1,D2,D3和D4),其中光电二极管堆叠在彼此之上,以生成用于与光电二极管相对应的放大器的电流差分信号,其中电流差分信号的生成在放大之前从光学信号中移除不期望的分量；以及炎症检测单元(136),被配置为接收来自对应的放大器的输出并且检测在组织区域处的炎症。(A system (100) for detecting tissue inflammation, in particular gingivitis, comprising: a light emitter (102) configured to emit light at a tissue region within a mouth of a user; at least four wavelength-sensitive photodetectors (110, 112, 114, and 116) configured to detect optical signals diffusely reflected by the tissue region, each of the at least four wavelength-sensitive photodetectors comprising a filter (BPF1, BPF2, BPF3, and BPF4) and a photodiode (D1, D2, D3, and D4), wherein the photodiodes are stacked on top of each other to generate a current differential signal for an amplifier corresponding to the photodiode, wherein the generation of the current differential signal removes undesired components from the optical signal prior to amplification; and an inflammation detection unit (136) configured to receive an output from the corresponding amplifier and detect inflammation at the tissue region.)

1. A system (100) for detecting tissue inflammation, comprising:

a light emitter (102) configured to emit light at a region of tissue (104) within a mouth of a user;

at least four wavelength-sensitive photodetectors (110, 112, 114, and 116) configured to detect optical signals diffusely reflected through the tissue region, each of the at least four wavelength-sensitive photodetectors comprising a filter (BPF1, BPF2, BPF3, and BPF4) and a photodiode (D1, D2, D3, and D4), wherein the photodiodes are stacked on top of each other to generate a current differential signal for an amplifier corresponding to the photodiode, wherein the generation of the current differential signal removes undesired components from the optical signal prior to amplification; and

a inflammation detection unit (136) configured to receive an output from the corresponding amplifier and detect tissue inflammation at the tissue region.

2. The system of claim 1, wherein the tissue inflammation detected is gingivitis.

3. The system of claim 1, wherein the light emitter and the at least four wavelength sensitive photodetectors are implemented in a Diffuse Reflectance Spectroscopy (DRS) probe having a source-detection distance between 300-2000 μ ι η.

4. The system of claim 1, further comprising a splitter (108), the splitter (108) configured to distribute the reflected light over the at least four wavelength sensitive photodetectors.

5. The system of claim 4, wherein the splitter is a fused fiber splitter, a dispersion splitter, or a light guide manifold.

6. The system of claim 1, wherein the light emitters are phosphor-converted white LEDs.

7. The system of claim 1, wherein the filter for each of the at least four wavelength-sensitive photodetectors is a band-pass filter.

8. The system of claim 1, wherein the magnitude of the current differential signal for the photodiodes (D1, D2, D3, and D4) is incremented.

9. The system of claim 1, wherein the current differential signals for the photodiodes (D1, D2, D3, and D4) include a first current differential signal, a second current differential signal, and a third current differential signal for photodiodes (D1, D2, and D3), respectively, wherein the second current differential signal is greater than the first current differential signal and the third current differential signal.

10. The system of claim 1, wherein the stacked photodiodes form a stack with a bottom photodiode, and the bottom photodiode is terminated with a current source controlled in a closed loop.

11. The system of claim 1, wherein the stacked photodiodes form a stack with a bottom photodiode, and the bottom photodiode generates a photocurrent at a level to minimize a maximum differential signal to be minimized.

12. A method for detecting tissue inflammation comprising a front end, comprising the steps of:

emitting (S220) light by a light emitter (102) towards a tissue region in a user' S mouth;

detecting (S230) an optical signal diffusely reflected by the tissue region via at least four wavelength sensitive photodetectors (110, 112, 114 and 116), each of which comprises a filter (BPF1, BPF2, BPF3 and BPF4) and a photodiode (D1, D2, D3 and D4), wherein the photodiodes are stacked on top of each other to generate a current differential signal for an amplifier corresponding to the photodiode, wherein the generation of the current differential signal removes undesired components from the optical signal prior to amplification;

inputting (S240) an output of the amplifier to an AD converter; and

inputting (S250) an output of the AD converter to a tissue inflammation detection unit.

13. The method of claim 12, wherein the tissue inflammation detected is gingivitis.

14. The method of claim 12, wherein the detecting step further comprises: distributing the reflected light over the at least four wavelength sensitive photodetectors (110, 112, 114, and 116) with a splitter.

15. The method of claim 14, wherein the splitter is a fused fiber splitter, a dispersion splitter, or a light guide manifold.

Technical Field

The present disclosure relates generally to a method for detecting the front end of tissue inflammation, particularly gingivitis, using diffuse reflectance spectroscopy.

Background

Currently, gingivitis detection using Diffuse Reflectance Spectroscopy (DRS) is performed with a small, angled probe that is deployed around one or more optical fibers that transmit light due to the limited space in the oral cavity. Such a small probe is useful for measuring at the interproximal areas where gingivitis usually originates. However, such small probes may exert a greater pressure on the tissue when in contact, pushing the blood aside, thereby disrupting the DRS measurement of blood properties. Therefore, DRS measurements are preferably performed in a non-contact mode, and the required non-contact mode results in detection of specularly reflected light in addition to the required diffuse reflection component. Since diffuse reflected light (i.e., light propagating through tissue) is highly attenuated, these specular components can become relatively large.

Furthermore, an important property of the probe is the source-detection separation, as it affects the sampling depth of the probe (i.e. the depth at which the measured light originates in the tissue). However, source-detection separation increases the risk of illuminating and/or detecting light from non-gingival tissue (e.g., teeth and/or dental implants). For example, because the nipple (papillalla) ends in a small tip, the desired nipple signal may be at least partially contaminated by the enamel signal due to fiber optic separation. Since the teeth and/or dental implants/restorations mainly exhibit a white/yellowish color, the wrong dental reflection will add a Direct Current (DC) -like offset to the DRS signal that does not contain information about gingivitis detection (i.e. hemoglobin concentration). The error signal occupies a portion of the dynamic range. Typically, such error signals are removed by appropriate signal processing after amplification and/or analog-to-digital conversion requiring a large dynamic range and requiring analog-to-digital converter resolution.

Accordingly, there is a need in the art for an inventive oral care system and method to enable accurate detection of tissue inflammation, particularly gingivitis, using a DRS front end that removes a large offset portion prior to amplification and/or analog-to-digital (AD) conversion, thereby relaxing the requirements for electronics.

Disclosure of Invention

The present disclosure relates to inventive systems and methods for detecting tissue inflammation, particularly gingivitis, using Diffuse Reflectance Spectroscopy (DRS). Various embodiments and implementations herein relate to a gingivitis detection system including a front end that provides a large dynamic range and that directly removes (i.e., at the sensor, before the sensor front end electronics) specular reflection components and DC components. Gingivitis detection systems include a specialized configuration of light emitters, more than four wavelength sensitive photodetectors, and a tissue inflammation detection system.

In general, in one aspect, a system for detecting tissue inflammation is provided. The system comprises: a light emitter configured to emit light at a tissue region within a mouth of a user; at least four wavelength sensitive photodetectors configured to detect an optical signal diffusely reflected by the tissue region, each of the at least four wavelength sensitive photodetectors comprising a filter and a photodiode, wherein the photodiodes are stacked on top of each other to generate a current differential signal for an amplifier corresponding to the photodiode, wherein the generation of the current differential signal removes undesired components from the optical signal prior to amplification; and a inflammation detection unit configured to receive an output from the corresponding amplifier and detect tissue inflammation at the tissue region. In various embodiments, the tissue inflammation is gingivitis.

In one embodiment, the light emitter and at least four wavelength sensitive photodetectors are implemented in a DRS probe having a source-detection distance between 300 μm-2000 μm.

In one embodiment, the system further comprises a splitter configured to distribute the reflected light over the at least four wavelength sensitive photodetectors.

In various embodiments, the splitter is a fused fiber splitter, a dispersive splitter, or a light guide manifold.

In one embodiment, the light emitters are phosphor-converted white LEDs.

In one embodiment, the filter for each of the at least four wavelength sensitive photodetectors is a band pass filter.

In one embodiment, the magnitude of the current differential signal for the photodiode is increasing.

In one embodiment, the current differential signals for the photodiode include a first current differential signal, a second current differential signal, and a third current differential signal for the photodiode, respectively, wherein the second current differential signal is greater than the first current differential signal and the third current differential signal.

In one embodiment, the stacked photodiodes form a stack with a bottom photodiode, and the bottom photodiode is terminated with a current source controlled in a closed loop.

In one embodiment, the stacked photodiodes form a stack with a bottom photodiode, and the bottom photodiode generates a photocurrent at a level to minimize the maximum differential signal to be minimized.

In general, in another aspect, a method for detecting tissue inflammation including a front end is provided. The method comprises the following steps: emitting light by a light emitter to a tissue region in a user's mouth; detecting an optical signal diffusely reflected by the tissue region via at least four wavelength-sensitive photodetectors, each of the at least four wavelength-sensitive photodetectors comprising a filter and a photodiode, wherein the photodiodes are stacked on top of each other to generate a current differential signal for an amplifier corresponding to the photodiode, wherein the generation of the current differential signal removes undesired components from the optical signal prior to amplification; inputting the output of the amplifier to an AD converter; and inputting an output of the AD converter to the tissue inflammation detection unit. In various embodiments, the tissue inflammation is gingivitis.

In one embodiment, the detecting step further comprises: the reflected light is distributed over at least four wavelength sensitive photodetectors using a splitter.

In one embodiment, the splitter is a fused fiber splitter, a dispersive splitter, or a light guide manifold.

As used herein for the purposes of this disclosure, the term "controller" is used generally to describe various devices relating to the operation of an imaging device, system or method. The controller can be implemented in numerous ways (e.g., such as with dedicated hardware) to perform the various functions discussed herein. A "processor" is one example of a controller employing one or more microprocessors that are programmed using software (e.g., microcode) to perform the various functions discussed herein. The controller may be implemented with or without a processor, and may also be implemented as a combination of dedicated hardware for performing some functions and a processor (e.g., one or more programmed microprocessors and associated circuitry) for performing other functions. Examples of controller components that may be employed in various embodiments of the present disclosure include, but are not limited to, conventional microprocessors, Application Specific Integrated Circuits (ASICs), and Field Programmable Gate Arrays (FPGAs).

It should be understood that all combinations of the foregoing concepts and additional concepts discussed in greater detail below (provided that these concepts do not contradict each other) are considered a part of the inventive subject matter disclosed herein. In particular, all combinations of claimed subject matter appearing at the end of this disclosure are considered part of the inventive subject matter disclosed herein.

These and other aspects of the invention will be apparent from and elucidated with reference to the embodiments described hereinafter.

Drawings

In the drawings, like reference numerals generally refer to like parts throughout the different views. Moreover, the drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the invention.

FIG. 1A is a graph of diffuse reflectance spectroscopy spectra measured at different probe-target angles, according to one embodiment.

Fig. 1B is a graph of calculated blood oxygenation blood values, according to one embodiment.

FIG. 2 is a diagram of simulated changes in diffuse reflectance spectroscopy spectra resulting from a change in tissue oxygenation from fully oxygenated to fully deoxygenated, according to one embodiment.

FIG. 3 is a schematic representation of a tissue inflammation detection system, according to an embodiment.

Fig. 4 shows a schematic block diagram of a tissue inflammation detection system comprising four wavelength sensitive photodetectors, according to an embodiment.

Fig. 5 is a flow diagram of a method for detecting tissue inflammation, according to an embodiment.

Detailed Description

The present disclosure describes various embodiments of systems and methods for using diffuse reflected light to improve detection of tissue inflammation, particularly gingivitis. More generally, applicants have recognized and appreciated that it would be beneficial to provide a system that removes large shifts as early as possible after acquisition of a diffuse reflectance spectral signal. Accordingly, the systems and methods described or otherwise contemplated herein provide an oral care device configured to obtain measurements of gingival tissue. The oral care device includes a light emitter and four or more wavelength sensitive photodetectors configured to detect diffusely reflected light such that the lowest possible current difference is received by an associated amplifier. By removing the large offset portion prior to amplification and/or analog-to-digital (AD) conversion, the requirements for electronics are relaxed and more accurate gingivitis detection is enabled.

The embodiments and implementations disclosed or otherwise contemplated herein may be utilized with any suitable oral care device, such as a toothbrush, a flossing device, an oral irrigator, a tongue cleanser, or other personal care device. However, the present disclosure is not limited to these oral care devices, and thus the disclosure and embodiments disclosed herein may encompass any oral care device.

Gingivitis, which is an inflammation of the gums characterized by swelling, swelling and redness of the gums, is primarily caused by plaque build-up, mostly in the gingival sulcus (pocket). Such gum disease is often found in hard-to-reach areas, such as the interproximal and posterior periodontal spaces between teeth.

In fact, it is estimated that 50% -70% of the adult population is affected by gingivitis. However, consumers are often unable to detect early signs of gingivitis. Normally, gingivitis develops until the individual finds their gums bleeding easily when brushing their teeth. Therefore, gingivitis can only be detected when the disease has progressed and is significantly more difficult to treat. Although gingivitis can be easily reversed by improving oral hygiene, it is important to maintain good oral health and detect gingivitis as quickly as possible, since gingivitis can spread to irreversible periodontitis.

Gingivitis can be diagnosed visually by detecting redness and swelling of the gums. (see RR. Lobene et al, "A modified gingival index for use in clinical trials", Clin. Prev. Dent.8:3-6, (1986) which describes a non-contact gingivitis index based on redness and inflammation of the gums). However, this has a limited sensitivity and is highly dependent on the color rendering index of the light source used. Thus, modern phosphor-converted LEDs may have a low CRI, resulting in poor visual judgment.

Redness of the gums is an acute inflammatory response to bacterial biofilm toxins from plaque in the gingival sulcus or along the gum line area. This inflammatory response causes vasodilation in the short term, where smooth muscle cells in the arterioles relax and widen the blood vessels to increase the blood supply to the capillary bed. This results in redness of the gums and can result in small temperature increases that are difficult to measure. In addition, the capillaries become more permeable, which results in increased fluid loss from the capillaries to the interstitial spaces, resulting in swelling of the gums. If the inflammation is chronic, additional redness occurs through increased vascularization of the tissue, where additional capillaries can be formed to address the additional blood demand of the tissue.

These factors enable detection of gingivitis based on Diffuse Reflectance Spectroscopy (DRS). DRS is an optical method that involves, for example, emitting white light toward a target and analyzing the spectral properties of the diffusely reflected (rather than specularly reflected) light. Due to the different chromophores in the gingival tissue, the spectral properties of the diffusely reflected light are significantly different from the spectral properties of the source light. For example, T.Handoka et al, "hepatoglobin conservation and oxyden preservation of clinical health and inflamed girbiva in human subjects", J.Periodonal Res.25: 93-98(1990), the increase in total hemoglobin concentration and decrease in blood oxygenation associated with gingivitis detection can be determined. The method uses six fixed wavelengths and calculates deoxygenation, oxygenation, and total hemoglobin concentration. The latter two are used to calculate oxygen saturation.

Fig. 1A and 1B show measured DRS spectra using different probe-target angles. In fig. 1B, blood oxygenation values were calculated according to the exemplary method described by Hanioka et al. For angles close to the surface normal, the specular reflection becomes about ten times the diffuse component. Therefore, as shown in fig. 1B, the oxygenation values calculated according to this method produce large variations. The detected specular reflected light may cause large errors.

Referring to fig. 2, it is evident that oxygenation-dependent changes in the DRS signal can become very small (even without errors and/or specular reflections), especially when Near Infrared (NIR) wavelengths are forced to be used due to sampling depth requirements. Fig. 2 shows simulated changes in DRS spectra caused by a change in tissue oxygenation from fully oxygenated to fully deoxygenated (100% (> 0%). In fact, the changes will be much smaller: for gingivitis, oxygenation is expected to be reduced by about 10%. There is no specular reflection.

According to embodiments using wavelength detection, some systems include a spectrometer to analyze the spectral shape of received light. Other systems include tunable filters (e.g., MEMS Fabry-perot filters) on the received and/or emitted light. While it is desirable to use spectrometers or tunable filters due to the large number of wavelengths available for processing, currently available systems are too large and/or too expensive for consumer products. Alternatively, the received light can be split into different paths, and band pass filters can be applied to achieve the desired spectral bands. The aforementioned Hanioka method uses six wavelengths and can be easily implemented using an embodiment of splitting light as long as a large offset is removed before AD conversion. If not removed, a large dynamic range and analog-to-digital converter resolution are required.

Since detection of gingivitis is based on changes in hemoglobin concentration, the signal resulting from these changes includes a small modulation of the larger offset fraction caused by other tissue scattered signals (gum and hard tooth tissue) and specular reflections. The offset part is not DC due to the movement; for example, very small angle changes may result in a large specular component. Therefore, the offset portion cannot be removed by high-pass frequency filtering. Due to the large offset, a large portion of the dynamic range of the front-end amplifier and the analog-to-digital (AD) converter resolution is wasted.

Based on the above, a particular object with certain embodiments of the present disclosure is to provide a DRS front-end that can remove wasted large offsets in the signal chain as early as possible.

Referring to fig. 3 and 4, in one embodiment, a system 100 for detecting tissue inflammation is provided. The system 100 is configured to remove large offsets prior to amplification and/or AD conversion. The system 100 includes an optical emitter (e.g., optical fiber) 102, an optical detector (e.g., optical fiber) 106, and a controller 130. In an example embodiment, the light emitter comprises a light source 103, for example, a broadband light source 103, such as a phosphor-converted white light LED. A light source is coupled into the source fiber to deliver the emitted light to the gingival tissue 104. A light detector (e.g., an optical fiber) 106 is configured to pick up diffusely reflected light from the tissue 104 and deliver the light.

In one embodiment, the optical emitter 102 and the optical detector 106 are implemented with a Diffuse Reflectance Spectroscopy (DRS) probe having a source-detector distance between 300 μm-2000 μm. Conventional configurations include: one source fiber followed by one detector fiber, a central source fiber surrounded by multiple detector fibers, or a single fiber serving as both a source and a detector. An important property of the probe is source-detection separation, as it affects the sampling depth of the probe (i.e., the depth at which the measured light originates in the tissue). To detect gingivitis, a mean diffuse reflectance spectroscopy sampling depth of greater than 250 μm is required. To obtain such an average, a minimum source-detector distance of about 300 μm is required, depending on the wavelength.

Since the DRS signal from detector 106 is typically not a differential signal, it includes additional components. According to one embodiment, the detector 106 of the system 100 is configured to deliver the reflected light to a spectral analysis unit or splitter 108. The splitter 108 is configured to distribute the reflected light over more than four wavelength sensitive photodetectors 110, 112, 114, and 116, each having a different wavelength sensitivity. The splitter 108 may be a fused fiber splitter, a dispersion splitter (e.g., a prism or grating), a light guide manifold, or any suitable alternative.

Each wavelength sensitive detector 110, 112, 114 and 116 includes a Band Pass Filter (BPF) in front of the photodiode. As shown in fig. 4, the detector 110 includes a band pass filter BPF1 in front of the photodiode D1. Similarly, detector 112 includes a band pass filter BPF2 in front of photodiode D2, detector 114 includes a band pass filter BPF3 in front of photodiode D3, and detector 116 includes a band pass filter BPF4 in front of photodiode D4. Photodiodes are advantageous because they have an extended linear range and can therefore process signals that include large offsets without introducing errors. Although the embodiment of fig. 4 includes four wavelength sensitive detectors, other embodiments may include five wavelength sensitive detectors or more than five wavelength sensitive detectors.

The photodiodes D1, D2, D3 and D4 are stacked such that the associated amplifiers receive a current differential, i.e., they receive a much smaller current. This enables greater amplification, which results in a higher and improved signal-to-noise ratio (SNR) for detection of gingivitis.

According to one embodiment, the current I₁...I_nArranged in increasing magnitudes. Alternatively, the current I₁...I_nArranged with a reduced amplitude. According toIn another embodiment, the current is arranged as follows I₁<I₂>I₃<I₄>I₅Etc. (or in other ways). However, the currents are never arranged such that the maximum and minimum expected currents are stacked on top of each other. According to one embodiment, the bottom of the stack is terminated by a current source, optionally controlled in a closed loop via controller 130. Alternatively, in the middle of the photodiode, the bottom diode produces the lowest desired photocurrent. According to another embodiment, the bottom diode generates a photocurrent at a level selected to minimize the largest of the differences to be minimized, for example, at a wavelength that is expected to give an output close to the average/median level.

Referring to fig. 4, according to one embodiment, the current difference present at the current-voltage amplifier is nominally (nominal) minimal and/or balanced around zero. According to another embodiment, in the case of a single supply electronic device, the current differential is a predetermined offset. As shown, the output of each wavelength sensitive photodetector is input to a corresponding amplifier. According to one embodiment, the output of the amplifier is fed to an AD converter (not shown) and the useful resolution is much higher because those signals also do not carry large offsets. Alternatively, the AD converter may have a lower resolution, which is advantageously cheaper.

The output of the AD converter is input to a controller or analyzer having a suitable gingivitis detection algorithm. According to one embodiment, the algorithm includes a gingivitis detection method based on a wavelength derivative (slope) signal. According to another embodiment, the algorithm includes a differential method for calculating tissue oxygenation, as described in DE Myers et al, "non-biological method for measuring local hemoglobin metabolism in tissue use with a gap second differentiated near-isolated spectroscopy", J.biomed.Opt., Vol.10(3), (2005). In Myers, a simple continuous wave near infrared algorithm is described using a single depth attenuation measurement at 680nm, 720nm, 760nm and 800 nm. However, the differential current configuration of the spectral detector as described above does not necessarily deliver the same differential as the derivative method requires. For example, if the methods require attenuation measurements at 680nm, 720nm, 760nm and 800nm, it is not necessary to stack the corresponding detectors on top of each other. Since the bottom current is known, all currents and hence the new difference can be calculated internally. This means that the stacking order can be chosen such that the current flowing into the amplifier is as low as possible. This enables a higher dynamic range.

Referring to fig. 5, in one embodiment, fig. 5 is a flow diagram of a method 200 for detecting tissue inflammation that includes a front end for directly removing a specular component and a DC component. In other words, the specular reflection and the DC component are removed at the sensor and before the sensor front end electronics. In step S210, a system for detecting tissue inflammation, particularly gingivitis, is provided. The system may be any device or system described herein or otherwise contemplated. For example, the system may be the system 100, among many other devices or systems. In general, the system includes a light emitter 102, four or more wavelength sensitive photodetectors 106, and a controller 130, the controller 130 configured to implement the functions described herein. Many other components and configurations are possible.

At step S220 of the method, the at least one light emitter 102 emits light, a beam of which impinges on the tissue. The light emitted by the light emitter may comprise two or more wavelengths. Thus, the light emitter may comprise one or more light sources 103. The light emitter may emit light periodically or continuously, or may emit light only in response to a trigger. For example, the system detects gingival tissue and activates the light emitter 102 to emit light.

At step S230 of the method, the reflected light is distributed over four or more wavelength sensitive photodetectors 106, the four or more wavelength sensitive photodetectors 106 each having a different wavelength sensitivity. According to one embodiment, the system 100 includes a splitter 108 configured to distribute the reflected light. Splitter 108 may be a fused fiber splitter, a light guide manifold, or any suitable alternative. The output of each wavelength sensitive photodetector is input to a corresponding amplifier.

At step S240 of the method, the output of the amplifier is fed into an AD converter. As mentioned above, the useful resolution is much higher since those signals also do not carry large offsets.

At step S250 of the method, the output of the AD converter is input to the controller 130 or processor, which controller 130 or processor is configured to analyze the signal. According to one embodiment, the controller 130 receives signals, which are analyzed by the processor 132 and/or the gingivitis detection unit 136 and/or stored in the memory 134 for future analysis.

Advantageously, the inventive systems and methods described herein remove large offsets as early as possible after acquisition of a diffuse reflectance spectral signal so that the associated amplifier receives the lowest possible current differential. By removing large offset portions prior to amplification and/or analog-to-digital (AD) conversion, the requirements for electronics are relaxed and more accurate gingivitis detection is enabled.

All definitions, as defined and used herein, should be understood to control dictionary definitions, definitions in documents incorporated by reference, and/or ordinary meanings of the defined terms.

The indefinite articles "a" and "an" as used herein in the specification and in the claims should be understood to mean "at least one" unless clearly indicated to the contrary.

The phrase "and/or" as used herein in the specification and claims should be understood to mean "either or both" of the elements so combined, i.e., the elements present in combination in some cases and present separately in other cases. Multiple elements listed with "and/or" should be understood in the same way, i.e., "one or more" of the elements so combined. Optionally, other elements may be present in addition to the elements specifically identified with the "and/or" clause, whether related or unrelated to those elements specifically identified.

As used herein in the specification and claims, "or" should be understood to have the same meaning as "and/or" as defined above. For example, when items are separated in a list, "or" and/or "should be interpreted as being inclusive, i.e., including at least one of many elements or lists of elements, but also including more than one, and optionally, including additional unlisted items. It is only expressly stated that terms of the contrary, such as "only one" or "consisting of …" when used in a claim, are intended to refer to the inclusion of only one element from a plurality or list of elements. In general, when preceding terms that are exclusive (such as "any," "one," "only one," or "only one"), the term "or" as used herein should only be construed to indicate a unique alternative (i.e., "one or the other but not both").

As used herein in the specification and claims, the phrase "at least one" in reference to one or more lists of elements should be construed to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements, and not excluding any combinations of elements in the list of elements. This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase "at least one" refers, whether related or unrelated to those elements specifically identified.

It will also be understood that, unless explicitly indicated to the contrary, in any methods claimed herein that include more than one step or action, the order of the steps or actions of the method is not necessarily limited to the order in which the steps or actions of the method are recited.

In the claims, as well as in the specification above, all transitional phrases such as "comprising," including, "" carrying, "" having, "" containing, "" involving, "" holding, "" consisting of … and the like are to be understood to be open-ended, i.e., to mean including but not limited to. The transition phrases "consisting of …" and "consisting essentially of …" alone should be closed or semi-closed transition phrases, respectively.

While several inventive embodiments have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the function and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the inventive embodiments described herein. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the inventive teachings is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific inventive embodiments described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the inventive embodiments may be practiced otherwise than as specifically described and claimed. Inventive embodiments of the present disclosure are directed to each individual feature, system, article, material, kit, and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and/or methods, if such features, systems, articles, materials, kits, and/or methods are not mutually inconsistent, is included within the inventive scope of the present disclosure.